GHS-R1a activity suppresses synaptic function of primary cultured hippocampal neurons

Ghrelin is an orexigenic gastric hormone that promotes feeding behaviors and regulates energy homeostasis in both humans and rodents. Studies have reported intriguing yet conflicting roles that ghrelin and its receptor growth hormone secretagogue receptor 1a (GHS-R1a) play in regulating multiple brain functions, such as learning and memory; however, the underlying mechanism is largely unknown. In this study, we investigated the effect of ghrelin incubation and virus-mediated GHS-R1a overexpression on synaptic functions of primary cultured hippocampal neurons. Our results demonstrated that ghrelin pre-treatment for 24 h, with a concentration of either 4 nM or 200 nM, suppressed the frequency of miniature excitatory postsynaptic currents (mEPSCs), the frequency and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Similarly, GHS-R1a overexpression inhibited both the frequency and the amplitude of mEPSCs, and mIPSCs frequency. Moreover, our in vitro Ca²⁺-image study with Rhod-3AM reveals that ghrelin pre-treatment for either 3 h or 24 h suppressed glutamate-induced elevation of cytoplasmic [Ca²⁺]. Our findings thus suggest that GHS-R1a signaling inhibits synaptic function of hippocampal neurons, which may contribute to the blocking effect of ghrelin on memory formation.